The present invention concerns a novel process for preparing an aqueous composition in the form of a gel and to novel compositions which can be obtained from this process, especially compositions containing vesicles, in particular liposomes.
Water-soluble polymers have numerous applications in a wide variety of industrial fields such as cosmetics, enhanced oil recovery, and food additives.
They are often used to control the rheology of aqueous formulations, since only a little dry material is needed to produce highly viscous solutions or even gels. A particular class of those water-soluble polymers is associative water-soluble polymers.
Two recent works are cited here which particularly concern that type of polymer: xe2x80x9cWater Soluble Polymersxe2x80x9d, ACS Symposium Series 467, ed. Shalaby W Shalaby et al., Am. Chem. Soc. Washington (1991), pp. 82-200, and xe2x80x9cPolymers in Aqueous Mediaxe2x80x9d, ed. J. Edward Glass, Advances in Chemistry Series no. 223, Am. Chem. Soc. Washington D.C. (1989).
Associative polymers are polymers constituted by a hydrophilic main chain and hydrophobic side chains which are relatively few in number compared with the hydrophilic units of the main chain. Their behavior in solution is a result of competition between the hydrophobic and hydrophilic properties of their structure. The hydrophobic units tend to form aggregates constituting linkage points between the macromolecular chains.
From a rheological viewpoint, associative water-soluble polymers have a very high viscosifying power in water, retain their viscosity well in a saline medium, and exhibit reversible behavior under stress (rheofluidifying).
The study of aqueous systems containing polymers and surfactants is very important because of the numerous industrial applications in a wide variety of fields such as paint, cosmetics, or enhanced oil recovery.
In those systems, mixed polymer/surfactant aggregates can form, which are stabilized by different types of interactions: electrostatic interactions, dipolar interactions, or hydrogen bonds. Associative water-soluble polymers can interact more specifically with surfactants due to their hydrophobic portions.
The following publications: I. Iliopoulos et al., Langmuir 1991, 7, 617; and B. Magny et al., Prog. Colloid. Polym. Sci., 1992, 89, 118, show that the addition of a cationic, anionic, or non ionic surfactant to a hydrophobically modified sodium polyacrylate solution causes an increase in viscosity.
U.S. Pat. No. 4,432,881 describes an aqueous liquid medium with increased viscosity obtained by dispersing a water-soluble polymer containing hydrophobic pendant groups and a surfactant in that medium. The medium can in particular be used for enhanced oil recovery.
S. Evani and G. D. Rose, Proc. Am. Chem. Soc. Div. of Polym. Mater. Sci. and Eng., 1987, 57, 477 describes two systems which use reversible hydrophobic combinations to control the rheology respectively of paints containing latex and of aqueous fluids for enhanced oil recovery.
For the surfactant associative polymer couples concerned, those two documents show the favorable effect on the viscosity of the medium either of an increase in temperature or of an increase in the salt concentration in the medium.
Further, a number of studies have been devoted to the determination of interactions and phase transitions in water-surfactant systems as a function of temperature and surfactant concentration.
Particular interest has been taken in systems in which the surfactant is a polyethyleneglycol monoalkylether with formula:
H(CH2)i(OCH2CH2 )jOH 
hereinafter termed CiEj where i represents the number of carbon atoms in the alkyl chain and j represents the number of ethylene oxide groups contained in the polar head of the surfactant.
Those surfactants have the particular property of having a low segregation temperature: there is a temperature above which the micellar solution separates into two phases, one of which is dilute and the other of which is concentrated in surfactant. This temperature is termed the cloud temperature. This phenomenon is due to a reduction in hydration of the ethylene oxide groups when the temperature increases. As a result, the longer the ethyleneglycol chain, the higher the segregation temperature.
At relatively high temperatures and very low concentrations, liquid crystal phases are observed (which constitute a further specific property of those surfactants): a lamellar phase La, which persists up to very high dilutions (concentrations of the order of 1% by weight for C12E5), two phases L3 and La+ constitute bilayers, and finally several regions of liquidxe2x80x94liquid coexistence have been shown to exist.
Phase diagrams of the surfactants C12E3, C12E4 and C12E5 have been published in the literature (see D. G. Hall, J. T. Tiddy, xe2x80x9cAnionic Surfactants: Physical Chemistry of Surfactant""s Action; Schick, M. J., Ed., Marcel Dekker, New York 1987, pp 55-108). More recently, a study concerning the surfactant C12E5 has been published (see R. Strey, R. Schomxc3xa4ker, D. Roux, F. Nallet, V. Olsson, J. Chem. Soc. Faraday Trans., 1990, 86, 2253).
The C12E5/H2O system has been studied in detail, in particular by R. Strey et al., J. Chem. Soc. Faraday Trans., 1990, 86, 2253. It produces a lamellar phase up to a water content of 99% by weight within a narrow temperature range. This organised structure is readily evidenced by the fact that the sample appeared birefringing between crossed polarizers, and could be more precisely characterized by measuring radiation diffusion. Thus light diffusion measurements allowed the distance d separating two lamellae to be determined. For a volume fraction f=0.0125 of C12E5, d was of the order of 3xc3x97107 m (3000 xc3x85). Further, since the repeat distance between lamellae was of the same order as the wavelength of visible light, the sample illuminated by white light appeared colored due to Bragg reflection.
The phase L3 which appears on the phase diagrams is often termed the abnormal or sponge phase. It may be birefringent on stirring and highly opalescent. Those characteristics are more marked when the solution is diluted. Its structure is defined as a continuous three dimensional bilayer. The bilayers constitute a type of randomly connected network which divides the volume of the solution into two equal parts.
The existence of another phase containing bilayers, the Lxcex1+ phase, has recently been reported by Jonstrxc3x6mer and Strey, J. Phys. Chem., 1992, 96, 5993. It has been observed in surfactants such as C12E3, C12E4, and C14E5, and its exact structure is currently unknown. It has the optical appearance of the L3 phase, i.e., it can be birefringent on stirring in some cases, but it is often more viscous than the L3 phase.
Its zone of existence is completely enclosed in that of the lamellar phase. The borders between the La and La+ phases are, further, difficult to determine insofar as the relaxation time at the end of which birefringence disappears after stirring has ceased can be relatively long.
The La+ phase can currently be defined as a dispersion of bilayers: either in the form of vesicles (simple or multilayered), or in the form of a diphase system in which there is an equilibrium between a lamellar phase and an aqueous phase. The structure remains to be precisely determined.
We have carried out systematic studies, in particular on aqueous compositions containing non ionic surfactants and associative polymers, and surprisingly, we have discovered perfect correlation between the gelling conditions of such systems and those for the appearance of a phase corresponding to bilayers in the phase diagram of the surfactant alone in solution in water.
Our discovery has led us to define a novel process which forms the subject matter of the present invention and, in order to obtain a composition in the form of a gel containing an associative polymer at a given temperature, consists in selecting a surfactant which at that temperature is in the form of bilayers in aqueous solution.
This discovery has also led us to define novel compositions which can be obtained using the process of the invention and in which the surfactant can form liposomes or vesicles.
Thus in a first aspect, the invention provides a process for preparing an aqueous composition in the form of a gel at a given temperature, characterized in that an associative water-soluble polymer constituted by a hydrophilic main chain and hydrophobic pendant groups is brought into the presence, in said composition, of at least one surfactant which is in the form of bilayers when it is in aqueous solution under the same temperature and concentration conditions.
As seen above, some surfactants have been studied in detail as regards their phase diagrams in aqueous solution. For these surfactants, reference is made to the data in the literature in order to determine the conditions in which they are in the form of bilayers. For other surfactants or aqueous media containing components other than the surfactant, which components can modify the phase transition temperature, the phase diagram is determined experimentally in order to determine the conditions under which the surfactants are in the form of bilayers.
The skilled person will, of course, search for birefringence zones which indicate the existence of a bilayer zone before making detailed determinations of the phase diagram.
In order to ensure the presence of bilayers, a radiation diffusion study can be carried out (using light, neutrons, X rays . . . ). Electron microscopy (cryofracture) can also be used to confirm the presence of vesicles and/or liposomes.
In a first variation of the invention, the bilayers form lamellar phases, which may or may not be dispersed.
In the particular case of polyethyleneglycol alkylether type surfactants, in an example in the literature dilute solutions of C12E4 (0.5% to 10%) exhibit separation into two isotropic liquid phases for temperatures in the range 6xc2x0 C. to 20 xc2x0 C. and separation into a liquid phase and a lamellar phase in the range 20xc2x0 C. to 50xc2x0 C. Within that temperature range, gel compositions are formed with that type of surfactant.
When the surfactant is in the form of vesicles, such as liposomes, the gels of the invention are obtained by simple introduction of associative water-soluble polymers into the dispersion of vesicles such as liposomes.
Examples of these surfactants are soya or egg lecithin, saturated or unsaturated monoalkylethers of polyethyleneglycol or linear or branched polyglycerol, or any other ionic or non ionic surfactant which can form vesicles.
The associative polymers used in the process of the invention are all the associative polymers cited above.
The hydrophilic main chain of these polymers can, in particular, result from polymerisation of a hydrophilic monomer containing functions onto which hydrophobic chains can subsequently be grafted, for example acid functions.
This method of preparing associative polymers is described in particular in the Shalaby W. Shalaby publication cited above, which publication is incorporated in its entirety by reference.
A water-soluble polymer of natural origin, or a natural polymer rendered water-soluble by chemical modification, can also be used.
Associative polymers can also be formed by copolymerisation of hydrophilic monomers and hydrophobic monomers. These hydrophobic polymers, introduced into the reaction medium in a much smaller quantity than the hydrophilic polymers, generally comprise a fatty hydrocarbon chain. This method of preparation is described in the publication by S. Biggs et. al., J. Phys Chem. (1992, 96. pp 1505-11).
Examples of these polymers are acrylic polymers, polyethers, and polyosidic chains which may be partially substituted.
The hydrophilic main chain is constituted as described above by a succession of hydrophilic monomer units and a fraction of monomers carrying highly hydrophobic pendant groups.
The molar percentage of monomers carrying hydrophobic pendant groups is termed the modification percentage of the hydrophilic chain.
This degree is activity in the range 0.1% to 10%, preferably in the range 0.5% to 5%, and more preferably in the range 1% to 3%.
The hydrophobic pendant groups can be any hydrophobic pendant group which is conventionally used to prepare associative polymers. Preferably, the hydrophobic groups used comprise a backbone containing at least 8 carbon atoms, preferably 12 to 18 carbon atoms.
Particular examples of these hydrophobic groups are linear, branched, saturated or unsaturated hydrocarbon chains which may or may not contain cycles.
Preferred examples of hydrophobic groups are hydrocarbon chains, in particular alkyl chains, containing 8 to 28 carbon atoms, preferably 12 to 18 carbon atoms.
Modified units are advantageously in the form of an ether, ester or amide. This is particularly the case when the main chain of the associative polymer is an acrylic chain.
The associative polymers used in the process of the invention can have a mass average molar mass in the range 104 to 107, preferably in the range 105 to 106.
The concentration of associative polymer in the aqueous composition is generally in the range 0.5% to 10% by weight, when the polymer has a mass average molar mass of the order of 150,000. This concentration can, of course, be lower for a polymer with a larger average molar mass.
The surfactant can be any surfactant which can form bilayers at the temperature and under the conditions for preparing the gel.
It may be a non ionic surfactant, for example a polyethyleneglycol monoalkylether with general formula:
CiH2i+1(OCH2CH2)jOH 
which is symbolically represented as CiEj.
Preferably, i is in the range 8 to 18, more preferably 12 to 14, and j is in the range 1 to 10, preferably 3 to 5.
Surfactant C12E4 is of particular interest due to its thermal behavior.
It may also be a non ionic surfactant with general formula:
CiH2ixe2x88x921(OCH2CH2)jOH 
which is a polyethyleneglycol monoalkylether in which the alkyl chain contains one unsaturation. In this case, i is preferably in the range 12 to 24, more preferably i is 18; and j is in the range 1 to 20, preferably 10.
We may also have a polyglycerol monoalkylether, in particular with formula:
R0Oxe2x80x94[C3H5(OH)Oxe2x80x94]nxe2x80x94H 
in which:
i) C3H5(OH)O is one of the following structures, taken as a mixture or separately: 
ii) n is an average statistical value in the range 1 to 6;
iii) R0 represents:
a) a linear or branched, saturated or unsaturated aliphatic chain containing 12 to 30 carbon atoms; or a hydrocarbon-containing radical of a lanoline alcohol; or the residue of a long-chain xcex1-diol;
b) an R1CO residue, where R1 is a linear or branched aliphatic C11-C17 radical;
c) an R2xe2x80x94[OC2H3(R3)xe2x80x94] residue, where:
R2 has the meaning given in a) or b) for
OC2H3(R3)xe2x80x94 is one of the following structures, taken as a mixture or separately: 
where R3 has the meaning given in a) for R0; or it may be a linear or branched ether of polyglycerol containing two fatty chains.
The surfactant can also be an ionic surfactant.
Examples are soaps such as sodium oleate, lecithin such as soya or egg lecithin, quaternary ammonium derivatives such as dialkyldimethylammonium type compounds, the alkyl group being a fatty chain containing at least 8 carbon atoms. A particular example is dioctadecyldimethylammonium bromide.
One class of surfactants which is of particular interest to the invention is constituted by those which can form liposomes. Examples of these surfactants are phospholipids, and soya or egg lecithin.
In an advantageous variation of the invention, the aqueous compositions contain 0.1% to 20%, preferably 0.1% to 10% by weight of surfactant or of a mixture of surfactants.
In order to control bilayer formation, it may be of interest to use a mixture of surfactants rather than one surfactant, in particular a mixture of surfactants of the type CiEj. Such a mixture allows the hydrophobic nature of the system to be adjusted at will. Thus, for example, by progressively replacing C12E5 with C12E3, keeping the total concentration of the surfactant constant, the apparent hydrophobic nature of the water-surfactant mixture can be increased with the result that the temperatures corresponding to the different phase transitions are continuously reduced.
Thus the use of such mixtures can allow the phase transition temperatures of water-surfactant mixtures to be varied and as a result, the temperature at which a gel appears in the presence of an associative polymer can be varied.
An analogous result can be obtained by introducing a fatty alcohol into the composition to modify the phase transition temperature. An example of a fatty alcohol which can be used for this purpose is hexanol. The concentration is advantageously 0.1% to 2%.
Other substances can also be used to control bilayer formation. Particular examples are sterols, fatty alcohol or sterol phosphates, fatty alcohol or sterol sulfates, fatty acids, fatty amines, saponins, triterpene derivatives, ceramides, and sphingosines.
Depending on the nature of the surfactant, the process of the invention can be used:
either to prepare a composition containing an associative water-soluble polymer which is fluid at a relatively low temperature and which gels within a higher range of temperatures, which is the case for surfactants in which the phase diagram exhibits a lamellar phase in this temperature range, while it has a biphase zone at a lower temperature. Thus the invention provides a process for preparing a composition containing an associative water-soluble polymer which is fluid at a given temperature termed the lower temperature and which gels within a range of temperatures which is higher than said temperature, the process consisting in introducing a surfactant into said composition, said surfactant having a phase diagram which exhibits a lamellar phase zone in said range of temperatures and a biphase zone at the lower temperature;
or to gel a dispersion of vesicles, in particular liposomes, by introducing an associative polymer into said dispersion.
As seen above, the process of the invention provides a means of considerably varying the viscosity of an aqueous composition containing an associative polymer by introducing a surfactant into the composition and by selecting the conditions such that the surfactant is in the form of bilayers.
This process for increasing the viscosity of an aqueous composition has a particularly important application in stabilising aqueous suspensions of particles, particularly in stabilising suspensions used in cosmetics, paints, or food additives.
Thus in a further aspect, the invention concerns the application of the process described above to stabilising an aqueous suspension of liquid or solid particles.
Examples of suspensions of solid particles which can be stabilised using the process of the invention are any suspensions of particles with a dimension in the range 0.02 microns to 50 microns, more particularly suspensions of pigments, talcs, or micas. These particles may have been surface treated.
Particular examples of suspensions of liquid particles are emulsions, more particularly emulsions of droplets with dimensions in the range 0.05 microns to 10 microns, for example oil-in-water emulsions.
Examples of other suspensions of particles of the invention are dispersions which are organised in the form of bilayers such as lamellar phases, vesicles, or liposomes.
A particularly interesting use for the process of the invention is transforming a suspension of liposomes into a gel by introducing an associative water-soluble polymer into said suspension. The invention thus provides a means of stabilising a liposome suspension at any temperature.
Such liposome suspensions with increased viscosity constitute novel compositions and thus the invention also provides, as novel substances, compositions containing liposomes and an associative water-soluble polymer.
Other aims, features and advantages of the invention become clear from the following description which refers to a number of examples of preferred implementations which are given simply by way of illustration and which in no way limit the scope of the invention. In the examples, all the percentages are given by weight unless indicated otherwise.